Synthesis of 2-phenyl-5,6-dihydropyrano[2,3-c]pyrrole-4,7-dione derivatives

Full text of DOI:10.1134/S1070363208080331

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 8, pp. 1641–1642. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © R.N. Vydzhak, S.Ya. Panchishin, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 8, pp. 1405–1406.
LETTERS
TO THE EDITOR
Synthesis of 2-Phenyl-5,6-dihydropyrano[2,3-c]pyrrole-
4,7-dione Derivatives
R. N. Vydzhak and S. Ya. Panchishin
Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 1, Kiev, 02660 Ukraine
e-mail: vydzhak@mail.ru
Received November 8, 2007
DOI: 10.1134/S1070363208080331
Pyrano[2,3-c]pyrroles constitute a poorly explored
class of fused heterocyclic compounds. We have found
only one publication where the synthesis of such
compounds containing an alkoxycarbonyl or carboxy
group in the 2-position has been described [1]. We
have developed a new synthetic approach to pyrano
[2,3-c]pyrrole-4,7-dione derivatives on the basis of
methyl (E)-6-phenyl-2,4-dioxohex-5-enoate (I) [2]. By
heating equimolar amounts of compound I, aromatic
aldehyde IIa or IIb, and 2-aminothiazole (III) in
glacial acetic acid for a short time we obtained the
corresponding 5-aryl-3-hydroxy-4-(3-phenylprop-2-
enoyl)-1-(1,3-thiazol-2-yl)-1,5-dihydro-2H-pyrrol-2-
ones IVa and IVb in moderate yield. Compounds of
type IV have been reported previously [3]. The
structure of pyrroles IVa and IVb was confirmed by
1
elemental analyses and IR and H NMR spectra. On
heating in DMSO in the presence of a catalytic amount
of iodine, compounds IVa and IVb underwent
intramolecular cyclization to 5-aryl-2-phenyl-6-(1,3-
thiazol-2-yl)-5,6-dihydropyrano[2,3-c]pyrrole-4,7-di-
ones Va and Vb, respectively. Such cyclization with
formation of pyran ring is used in the chemistry of
chromone [4, 5].
O
O
N
O
OMe
+
+
Ar
Ph
Ph
H2N
S
H
O
I
IIa, IIb
III
Ar
O
O
O
Ar
N
S
N
N
N
S
Ph
HO
O
O
IVa, IVb
Va, Vb
Ar = C6H5 (a), 4-ClC6H4 (b).
Compounds Va and Vb are colorless crystalline
substances which are sparingly soluble in acetic acid,
dioxane, benzene, and acetonitrile. The IR spectra
(KBr) contain three strong absorption bands in the
region 1600–1750 cm–1: 1620–1640, 1660–1680,
1710–1740 cm–1. No absorption was observed in the
region 3150–3600 cm–1, indicating that the cyclization
spectra of pyranopyrroles Va and Vb are consistent
with the assumed structure. The 5-H proton resonates
as a singlet at δ 6.30–6.50 ppm, and the 3-H signal
appeared as a singlet at δ 7.15–7.25 ppm.
The described procedure makes it possible to obtain
a wide series of 2-aryl-5,6-dihydropyrano[2,3-c]
pyrrole-4,7-dione derivatives which attract interest
1
involved the hydroxy group in IV. The H NMR
1641

VYDZHAK, PANCHISHIN
1642
from the viewpoint of the search for biologically active
compounds and the examine their chemical properties.
The scope of application of this method for building up
fused pyranone derivatives will be considered
elsewhere.
(to remove traces of iodine) and water, and recrystal-
lized from DMF–ethanol (3:1). Yield 42%, mp 288–
289°C. IR spectrum, ν, cm–1: 1630 (C=C), 1680
(C4=O), 1720 (C7=O). 1H NMR spectrum, δ, ppm: 6.37
s (1H, 5-H), 7.19 s (1H, 3-H), 7.25–7.65 m (10H,
Harom), 7.97–8.05 m (2H, Harom). Found, %: C 68.07; H
3-Hydroxy-5-phenyl-4-(3-phenylprop-2-enoyl)-1-
(1,3-thiazol-2-yl)-1,5-dihydro-2H-pyrrol-2-one (IVa).
A mixture of 0.01 mol of compound I, 0.01 mol of
benzaldehyde, and 0.01 mol of 2-aminothiazole in 15
ml of glacial acetic acid was heated for 20 min under
reflux. The mixture was cooled, and the precipitate
was filtered off, washed with 5 ml of acetic acid and
10 ml of ethanol, and recrystallized from DMF–
ethanol. Yield 42%, mp 246–247°C. IR spectrum, ν,
cm–1: 1600 (C=C), 1650 (C=O, ketone), 1690 (C=O,
lactam), 3250 (OH). 1H NMR spectrum, δ, ppm: 6.12 s
(1H, 5-H), 7.18–7.71 m (14H, Harom). Found, %: C
68.26; H 4.22; N 7.09; S 8.23. C22H16N2O3S.
Calculated, %: C 68.03; H 4.15; N 7.21; S 8.25.
3.81; N 7.24; S 8.55. C22H14N2O3S. Calculated, %: C
68.38; H 3.65; N 7.25; S 8.30.
5-(4-Chlorophenyl)-2-phenyl-6-(1,3-thiazol-2-yl)-
5,6-dihydropyrano[2,3-c]pyrrole-4,7-dione (Vb) was
obtained in a similar way. Yield 47%, mp 259–260°C
(from DMF–ethanol, 4:1). IR spectrum, ν, cm–1: 1630
(C=C), 1680 (C4=O), 1720 (C7=O). 1H NMR
spectrum, δ, ppm: 6.39 s (1H, 5-H), 7.21 s (1H, 3-H),
7.35–7.65 m (9H, Harom), 7.97–8.05 m (2H, Harom).
Found, %: C 63.02; H 3.35; Cl 8.69; N 6.81; S 7.87.
C22H13ClN2O3S. Calculated, %: C 62.78; H 3.11; Cl
8.42; N 6.66; S 7.62.
The IR spectra were recorded in KBr on a UR-20
1
spectrometer. The H NMR spectra were measured on
5-(4-Chlorophenyl)-3-hydroxy-4-(3-phenylprop-
2-enoyl)-1-(1,3-thiazol-2-yl)-1,5-dihydro-2H-pyrrol-
2-one (IVb) was synthesized in a similar way. Yield
45%, mp 242–243°C (from DMF–ethanol, 4:1). IR
spectrum, ν, cm–1: 1600 (C=C), 1650 (C=O, ketone),
1690 (C=O, lactam), 3200 (OH). 1H NMR spectrum, δ,
ppm: 6.07 s (1H, 5-H), 7.23–7.71 m (13H, Harom).
Found, %: C 62.77; H 3.61; Cl 8.30; N 6.49; S 7.66.
C22H15ClN2O3S. Calculated, %: C 62.49; H 3.58; Cl
8.38; N 6.62; S 7.58.
a Varian VXR-300 instrument from solutions in
DMSO-d6 using hexamethyldisiloxane as internal
reference.
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2,5-Diphenyl-6-(1,3-thiazol-2-il)-5,6-dihydropy-
rano[2,3-c]pyrrole-4,7-dione (Va). A catalytic amount
of iodine was added to a solution of 0.003 mol of
compound IVa in 15 ml of DMSO, and the mixture
was heated for 30 min under reflux. It was then diluted
with 50 ml of water, and the precipitate was filtered
off, washed with a 5% solution of sodium thiosulfate
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 8 2008